Kidney Week

Abstract: TH-PO432

Targeted Metabolomics of Adolescent CKD

Session Information

• Nutrition, Inflammation, Metabolism: Basic Mechanisms
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Nutrition, Inflammation, and Metabolism

• 1401 Nutrition, Inflammation, Metabolism

Authors

• Brooks, Ellen, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States

Ellen Brooks,

• Haymond, Shannon, Northwestern University, Chicago, Illinois, United States

Shannon Haymond,

• Langman, Craig B., Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States

Craig B. Langman,

• Warady, Bradley A., The Children's Mercy Hospital, Kansas City, Missouri, United States

Bradley A. Warady,

• Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Susan L. Furth,

Background

Dysregulation of amino acids, biogenic amines, and phosphatidylcholines (PCs) have been described in advanced chronic kidney disease (CKD) in adults. Metabolic alterations related to oxidative stress and inflammation in children with mild to moderate CKD may have greater significance for risk of secondary morbidities since growth and development are not complete.

Methods

In this cross-sectional study, 2 CKD groups were matched for age and gender but had differing measured (m)GFR by iohexol clearance and CKD stage [n=20 per CKD group with 10 glomerular (G) and 10 non-glomerular (NG) disorder per group]. Targeted plasma metabolomics were completed at the Proteomics and Metabolomics Shared Resource, Duke University (Durham, NC) using the Biocrates AbsoluteIDQ^® p180 panel-ultra-HPLC-tandem mass spectrometry and integrated software (Biocrates Life Sciences AG, Austria).

Results

The median (Md) and interquartile range (IQR) mGFR of the groups differed as planned: 74.3 (67.4, 82.9) CKD 2 vs. 32.8 (24.3, 35.5) ml/min/1.73m² CKD 3b (p<0.001) but age was similar 14.7 (11.7, 16.0) vs. 15.0 (12.7, 15.7) yrs. Plasma symmetric dimethylarginine (SDMA), creatinine, kynurenine (Kyn), sarcosine, trans-4-OH-proline, aspartic acid, alanine, and glycine were higher in CKD 3b (biogenic amines and amino acids p range=5.5E^-7 to 0.04) but long chain PCs were lower (p=0.01-0.035). In CKD 3b, SDMA/asymmetric DMA, Kyn/tryptophan (tryp), and phenylalanine/tryp were higher (p=6.79E-7 to 4.4E-4), Kyn was greater in NG vs. G (p=0.009) and alanine was higher in G vs. NG (p=0.045).

Conclusion

The aberrant metabolic patterns in adolescents with CKD 3b infer augmented amino acid catabolism, including alanine via pyruvate and tryp via indoleamine 2,3-dioxygenase 1 (IDO-1). The Kyn pathway is upregulated by IDO-1 and -2 in acute/chronic infection to inhibit bacterial growth and amplify immunosuppression, which may occur in CKD 3b NG. The higher SDMA and SDMA/ADMA ratio are likely related to decreased GFR while PC derangement may be due to phospholipase A₂ increased mass and activity. Low plasma PCs can result from PC accumulation in LDLs and may signify increased cardiovascular risk, while CKD-MBD may be related to enhanced collagen turnover. Correlations with clinical and biochemical parameters will provide further evidence of altered metabolomic contributions to the excess morbidity of pediatric CKD.